In this investigation the reaction properties of human sickle cell hemoglobin (Hb S) will be studied by means of measurements of oxidation-reduction potentials of ferrihemoglobin S/ferrohemoglobin S system. Previous investigations have shown that the oxidation reaction resembles oxygenation and other ligand equilibria in many respects, although not in all (e.g., cooperativity). The effects of variations in experimental conditions, such as pH and concentrations of organic phosphates or other ions, and of procedures and reagents which have been reported to influence the sickling phenomenon will be investigated. The latter include treatment with substituted amides, cynate, amino acids (glutamine, homoserine, arginine, phenyl alanine), various small peptides and sulfhydryl group reagents. Particular attention will be paid to observing whether the concentration of Hb S affects oxidation as it does oxygenation. The effects of these variables and procedures on oxygenation, on other ligand equilibria, and on the reaction properties of human adult hemoglobin (Hb A) or other hemoglobins whenever such controls are necessary or desirable.